Relative involvement of mu, kappa and delta receptor mechanisms in opiate-mediated antinociception in mice

Abstract

The antinociceptive properties of morphine (mu), ethylketazocine (kappa), nalorphine (kappa), [D-Ala2, D-Leu5]enkephalin (delta) and [D-Ala2, Met5]enkephalinamide (mu, delta) were assessed using the radiant heat tail-flick and acetic acid-induced writhing assays in mice. The apparent pA2 values for the interaction of naloxone with morphine were the same regardless of the nociceptive stimulus employed or the route of administration of morphine. The apparent pA2 values for the interactions of naloxone with ethylketazocine and nalorphine in the writhing test differed significantly from that for the interaction of morphine and naloxone. Nalorphine did not produce a consistent antinociceptive effect on the tail-flick test. The apparent pA2 values for the interaction of ethylketazocine (s.c. or i.c.v.) with naloxone were similar to those for morphine-naloxone interactions on the tail-flick assay. The apparent pA2 values for the interactions of naloxone with [D-Ala2, D-Leu5] enkephalin differed from those for morphine-naloxone interactions on the writhing test. The highly selective mu antagonist beta-funaltrexamine antagonized the agonist actions of morphine and [D-Ala2, D-Leu5]enkephalin, and, in a previous study, beta-funaltrexamine antagonized the antinociceptive actions of [D-Ala2, Met5]enkephalinamide, but not those of nalorphine. It was concluded that agonist interaction with mu or kappa receptors can result in antinociceptive effects in the acetic acid-induced writhing test, and that an agonist interaction with mu, but not kappa, receptors results in antinociceptive action on the radiant heat tail-flick test, and furthermore, that a possible combination of mu and delta receptor interaction can result in antinociceptive activity in both tests.